STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter

Zugowski, C; Lieder, Franziska; Müller, Annekatrin; Gasch, J; Corvinus, Florian; Moriggl, Richard; Friedrich, Karlheinz

doi:10.1515/bc.2011.038

Cited by 42 publications

(51 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Matrix metalloproteinase 1 (MMP-1) is associated with lung cancer growth and invasiveness [34], and STAT3 aberrantly induces the MMP-1 gene in colorectal carcinomas [35]. An assay with the MMP1 promoter placed in front of luciferase revealed that increasing amounts of SIAH2 repressed the activity of this reporter (Fig.…”

Section: Resultsmentioning

confidence: 99%

SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells

Muller¹,

Chen

Ginter³

et al. 2014

Oncotarget

Self Cite

View full text Add to dashboard Cite

The Janus tyrosine kinases JAK1-3 and tyrosine kinase-2 (TYK2) are frequently hyperactivated in tumors. In lung cancers JAK1 and JAK2 induce oncogenic signaling through STAT3. A putative role of TYK2 in these tumors has not been reported. Here, we show a previously not recognized TYK2-STAT3 signaling node in lung cancer cells. We reveal that the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK2. This mechanism consequently suppresses the activation of STAT3. In agreement with these data the analysis of primary non-small-cell lung cancer (NSCLC) samples from three patient cohorts revealed that compared to lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) show significantly higher levels of SIAH2 and reduced STAT3 phosphorylation levels. Thus, SIAH2 is a novel molecular marker for SCC. We further demonstrate that an activation of the oncologically relevant transcription factor p53 in lung cancer cells induces SIAH2, depletes TYK2, and abrogates the tyrosine phosphorylation of STAT1 and STAT3. This mechanism appears to be different from the inhibition of phosphorylated JAKs through the suppressor of cytokine signaling (SOCS) proteins. Our study may help to identify molecular mechanisms affecting lung carcinogenesis and potential therapeutic targets.

show abstract

Section: Resultsmentioning

confidence: 99%

SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells

Muller¹,

Chen

Ginter³

et al. 2014

Oncotarget

Self Cite

View full text Add to dashboard Cite

show abstract

“…The matrix metalloproteinase (MMP) family of proteases are zinc-dependent and are capable of degrading many types of extracellular matrix proteins and several family members are confirmed STAT3 target genes. MMP-1 was observed to be up regulated in a STAT3-dependent manner in human colorectal adenocarcinoma and urinary bladder transitional cell carcinoma cells [50,113]. The MMP1 gene was found to contain a STAT3 and an AP-1 binding site and mutation of either the STAT3 or AP-1 site ablated STAT3-mediated gene activation [50,113].…”

Section: Tumor Supporting Functions Of Stat3mentioning

confidence: 99%

“…MMP-1 was observed to be up regulated in a STAT3-dependent manner in human colorectal adenocarcinoma and urinary bladder transitional cell carcinoma cells [50,113]. The MMP1 gene was found to contain a STAT3 and an AP-1 binding site and mutation of either the STAT3 or AP-1 site ablated STAT3-mediated gene activation [50,113]. Further investigation revealed both STAT3 and c-Jun were directly bound to the MMP1 promoter in a manner dependent on c-Jun binding [50].…”

Section: Tumor Supporting Functions Of Stat3mentioning

confidence: 99%

STAT3 Target Genes Relevant to Human Cancers

Carpenter

2014

Cancers

419

395

View full text Add to dashboard Cite

Since its discovery, the STAT3 transcription factor has been extensively studied for its function as a transcriptional regulator and its role as a mediator of development, normal physiology, and pathology of many diseases, including cancers. These efforts have uncovered an array of genes that can be positively and negatively regulated by STAT3, alone and in cooperation with other transcription factors. Through regulating gene expression, STAT3 has been demonstrated to play a pivotal role in many cellular processes including oncogenesis, tumor growth and progression, and stemness. Interestingly, recent studies suggest that STAT3 may behave as a tumor suppressor by activating expression of genes known to inhibit tumorigenesis. Additional evidence suggested that STAT3 may elicit opposing effects depending on cellular context and tumor types. These mixed results signify the need for a deeper understanding of STAT3, including its upstream regulators, parallel transcription co-regulators, and downstream target genes. To help facilitate fulfilling this unmet need, this review will be primarily focused on STAT3 downstream target genes that have been validated to associate with tumorigenesis and/or malignant biology of human cancers.

show abstract

“…STAT3 regulates the transcription of MMP-1, which has been reported in colon cancer. STAT3 may directly act on MMP-1 or indirectly facilitate MMP-1 expression via activator protein (AP)-1 (a transcription factor) (11,25).…”

Section: Discussionmentioning

confidence: 99%

“…STAT3 may also facilitate the expression of matrix metalloproteinase (MMP) family members, including MMP-2 (9), MMP-7 (10) and MMP-9 (6), which have crucial roles in the invasion and metastasis of GC. There is evidence indicating that the expression of STAT3 and MMP-1 is increased in colon cancer, which exerts a promotive effect on the invasion and metastasis of GC (11,12). Studies have also demonstrated increased MMP-1 levels in peripheral blood in GC patients and elevated MMP-1 expression in GC tissues (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Expression of STAT3, MMP-1 and TIMP-1 in gastric cancer and correlation with pathological features

Cai

Wang

et al. 2012

Mol Med Report

View full text Add to dashboard Cite

Abstract. The aim of this study was to investigate the mRNA and protein expression of STAT3, MMP-1 and TIMP-1 in gastric cancer (GC), and to explore the correlations between these proteins and the biological behaviors of GC. Reverse transcription-polymerase chain reaction was employed to detect the mRNA expression of STAT3, MMP-1 and TIMP-1 in GC tissues (n=30), adjacent normal tissues (n=30) and superficial gastritis (SG) tissues (n=30). Immunohistochemistry was performed using the SP method to measure the protein expression of STAT3 (unphosphorylated), MMP-1 and TIMP-1. The correlation between the pathological features of GC and STAT3, MMP-1 as well as TIMP-1, were evaluated. The mRNA expression of STAT3 in GC tissues (0.821±0.128) was significantly higher compared to that in adjacent normal tissues (0.355±0.100) and SG tissues (0.398±0.096) (P<0.05). The mRNA expression of MMP-1 in GC tissues (0.749±0.133) was significantly increased compared to adjacent normal tissues (0.335±0.106) and SG tissues (0.345±0.063) (P<0.05). The mRNA expression of TIMP-1 in GC tissues (0.386±0.125) was comparable to that in adjacent normal tissues (0.343±0.078) and SG tissues (0.345±0.061), but the mRNA expression of TIMP-1 in GC tissues was significantly correlated with the differentiation of GC cells and lymph node metastasis. STAT3, MMP-1 and TIMP-1 were significantly associated with the differentiation of GC cells and lymph node metastasis, but not related to age, gender and tumor size. The positive rate of unphosphorylated STAT3 expression was dramatically higher in GC tissues (86.7%) compared to that in adjacent normal tissues (16.7%) and SG tissues (10.0%) (P<0.05). The positive rate of MMP-1 protein expression in GC tissues (63.3%) was significantly higher compared to that in adjacent normal tissues (13.3%) and SG tissues (16.7%) (P<0.05). However, no significant difference was observed in the TIMP-1-positive rate among the three groups (23.3, 16.7 and 10.0%, respectively; P>0.05). STAT3 and MMP-1 may be involved in the development and metastasis of GC, and treatment targeting TIMP-1 may be a promising strategy.

show abstract

STAT3 controls matrix metalloproteinase-1 expression in colon carcinoma cells by both direct and AP-1-mediated interaction with the MMP-1 promoter

Cited by 42 publications

References 32 publications

SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells

SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells

STAT3 Target Genes Relevant to Human Cancers

Expression of STAT3, MMP-1 and TIMP-1 in gastric cancer and correlation with pathological features

Contact Info

Product

Resources

About